1. Field of the Invention
The present invention concerns antimicrobial peptides and an antimicrobial agent. More specifically, it concerns an antimicrobial agent containing novel antimicrobial peptides, salts of these peptides, or a mixture thereof, as active components, a method for treating products which uses this antimicrobial agent, and an antimicrobial peptide compound containing an antimicrobial peptide, a salt of this peptide or a mixture of at least two of these salts, as active components.
In the specification of the present invention, the amino acids and peptides are represented by the abbreviations employed by IUPAC-IUB Committee on Biochemical Nomenclature, such as the following abbreviations.
Ala-: L-Alanine residue PA1 Arg-: L-Arginine residue PA1 Asn-: L-Asparagine residue PA1 Asp-: L-Aspartic acid residue PA1 Cys-: L-Cysteine residue PA1 Gln-: L-Glutamine residue PA1 Glu-: L-Glutamic acid residue PA1 Gly-: L-Glycine residue PA1 His-: L-Histidine residue PA1 Ile-: L-Isoleucine residue PA1 Leu-: L-Leucine residue PA1 Lys-: L-Lysine residue PA1 Mct-: L-Methionine residue PA1 Phe-: L-Phenylalanine residue PA1 Pro-: L-Proline residue PA1 Ser-: L-Serine residue PA1 Thr-: L-Threonine residue PA1 Trp-: L-Tryptophan residue PA1 Tyr-: L-Tyrosine residue PA1 Val-: L-Valine residue.
2. Description of Related Prior Art
Numerous inventions concerning peptides which possess antimicrobial properties against various microorganisms have so far been reported. Examples include a phosphonotripeptide (Japanese Patent Provisional Publication No. 106689/82), a phosphonodipeptide derivative (Japanese Patent Provisional Publication No. 13594/83) and a cyclic peptide derivative (Japanese Patent Provisional Publication No. 213744/83) effective against gram-positive and gram-negative bacteria, a peptide demonstrating an antimicrobial and antiviral action (Japanese Patent Provisional Publication No. 51247/84), a polypeptide effective against yeast (Japanese Patent Provisional Publication No. 130599/85), a saccharopeptide derivative effective against gram-positive bacteria (Japanese Patent Provisional Publication No. 172998/85, Japanese Patent Provisional Publication No. 251699/86, Japanese Patent Provisional Publication No. 44598/88), an oligopeptide effective against gram-positive bacteria (Japanese Patent Provisional Publication No. 22798/87), a peptidal antibiotic substance (Japanese Patent Provisional Publication No. 51697/87, Japanese Patent Provisional Publication No. 17897/88) as well as an antimicrobial peptide extracted from blood cells of North American king crabs (Japanese Patent Provisional Publication No. 53799/90) and an antimicrobial peptide isolated from blood lymph of honeybees (Japanese Patent Provisional Publication No. 500084/90).
On the other hand, lactoferrin, which is a natural iron-binding protein contained in tears, saliva, peripheral blood, milk etc. is known to demonstrate an antimicrobial activity against Escherichia coli, Candida, Clostridium, and other harmful microorganisms (Journal of Pediatrics, Vol. 94, p. 1, 1979).
The inventors of the present invention, in planning to cheaply isolate from nature a substance which possesses strong antimicrobial properties, which has no undesirable side effects (such as antigenicity) and is heat-resistant, focused on whey, a by-product of cheese manufacturing, and conducted research regarding the antimicrobial properties of the lactoferrin contained in it. They discovered that the catabolite of lactoferrin hydrolysis by an acid or an enzyme has stronger heat resistant and antimicrobial properties than the non-hydrolyzed lactoferrin, and have filed a patent application (Japanese Patent Application No. 13315/90). The composition and action of the antimicrobial substance present in such a lactoferrin hydrolysate have not been sufficiently understood, however, and therefore, the development of an effective antimicrobial agent had not yet been achieved.